Technetium-99m- or Cy7-Labeled Rituximab as an Imaging Agent for Non-Hodgkin Lymphoma

Abstract

Introduction: Rituximab was the first monoclonal antibody approved for the treatment of B-cell non-Hodgkin lymphoma (NHL) expressing CD20 antigen. This antibody has also the potential to be used as a specific fluorescent and radiolabel agent for targeting NHL. Objective: To radiolabel rituximab with technetium-99m (^99mTc) or Cy7 and evaluate both probes as potential imaging agents for NHL. Methods: Rituximab was derivatized with the trifluoroacetyl hydrazino protected form of succinimidyl ester of HYNIC and radiolabeled with ^99mTc. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and single-photon emission computed tomography/computed tomography (SPECT/CT) were performed. Raji cells were transfected with luciferase for bioluminescent NHL imaging up to 21 days. Rituximab was labeled with Cy7 for in vivo noninvasive fluorescence imaging up to 96 h. Results: Radiolabeling was carried out in a fast, reproducible, easy, and stable way with high radiochemical purity and did not interfere with epitope recognition. Biodistribution and SPECT/CT studies showed high liver and discrete tumor uptake. Bioluminescence and fluorescence studies helped us evaluate rituximab-Cy7 in Raji subcutaneous engraftment in BALB/c nude mice. Conclusions: Our results support the potential use of rituximab labeled either with ^99mTc or Cy7 as a molecular imaging tool for staging, restaging, and guiding surgical excision of tumors, which merits further evaluation.

Preparation and preliminary bioevaluation studies of 68Ga‐NOTA‐rituximab fragments as radioimmunoscintigraphic agents for non‐Hodgkin lymphoma

“…27 Camacho et al also made similar observations of slow pharmacokinetics and hepatic clearance with specific NHL imaging agent 99m Tc-Hynic-rituximab. 28,29 Hence, for radioimmunodiagnosis, use of short-lived 68 Ga-labeled fragmented MAbs may be considered due to their faster pharmacokinetics, rapid clearance from body, high tumor/blood ratios, favorable imaging kinetics, better tumor penetration, lower immunogenicity, and low nonspecific binding largely owing to their small size and absence of Fc region, as compared with the intact mAbs. [30][31][32] Fragmented MAbs also allow serial imaging within a day because of shorter plasma life than intact antibody.…”

Tracking of transplanted human umbilical cord-derived mesenchymal stem cells labeled with fluorescent probe in a mouse model of acute lung injury

“…A novel fluorescent molecule probe was first synthesized through the covalent coupling of anti-GD2 and fluorophore CyDye mono-reactive NHS esters (Cy7) ( 20 ). In the present study, according to the specific binding of antigen and antibody, synthetic anti-GD2-Cy7 wasincubated with hUC-MSCs in a standard culture medium ( 21 ). The labeled hUC-MSCs were transplanted into a lipopolysaccharide (LPS)-induced ALI mouse model to preliminarilyinvestigate the distribution processes of hUC-MSCs in treating ALI, which provides a theoretical basis for the establishment of an hUC-MSC treatment strategy for ALI in clinical work.…”

Monte Carlo dosimetry of a realistic multicellular model of follicular lymphoma in a context of radioimmunotherapy

“…Hence, the absorbed dose to the tumor delivered by radionuclides with short half-lives, such as 111 In and 90 Y, is overestimated compared to those with longer half-live. We note, however, that SPECT acquisitions of mice and patients showed early uptake of rituximab in NHL [76][77] (a few hours after administration while the physical half-lives of 111 In and 90 Y are~2 days). Regarding the elimination of the rituximab in NHL, no data were found in the literature.…”